REPATHA (EVOLOCUMAB) FOUR-YEAR OPEN-LABEL FOLLOW-UP STUDY PUBLISHED IN JAMA CARDIOLOGY Long-Term Study Identified No New Safety Concerns

THOUSAND OAKS, Calif. (March 14, 2017) – Amgen (NASDAQ:AMGN) today announced that four-year follow-up results from the Repatha (evolocumab) OSLER-1 study, the longest PCSK9 inhibitor clinical trial to date, were published in JAMA Cardiology. Repatha, when added to standard of care (SOC), achieved median low-density lipoprotein cholesterol (LDL-C) reductions of 57 percent at four years, with no new safety concerns identified and no neutralizing antibodies observed with cumulative exposure.¹

“For patients with cardiovascular disease, persistent LDL-C reduction is an important component of managing this chronic disease,” said Michael J. Koren, M.D., Jacksonville Center for Clinical Research. “These results reinforce that adding Repatha to the cardiovascular standard of care can achieve additional sustained LDL-C reductions over several years with no increased risk of safety concerns for patients who continue to struggle with elevated cholesterol levels.”

The OSLER-1 open-label extension (OLE) study enrolled 1,324 of the 1,650 (80.2 percent) eligible patients who completed a Phase 2 parent study. OSLER-1 evaluated the durability of LDL-C reduction and incidence of adverse events (AE) with long-term therapy with Repatha. Once therapy was initiated, 79 percent of patients persisted with Repatha treatment with average exposure duration of 44 months. Patients who reached four years of follow-up achieved a median LDL-C of 60 mg/dL.¹

“Safely reducing LDL-C over the long term is an important treatment objective given that many patients with elevated cholesterol will experience one or more cardiovascular events in their lifetime,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These long-term follow-up data reaffirm our conviction that Repatha is a valuable tool in the management of cardiovascular disease.”

The analysis found no new safety concerns with prolonged observation and reported that AEs occurred in 52.6 percent of patients treated with Repatha and SOC during year four compared to 79.3 percent during year one. The annualized AE rates in the Repatha and SOC group versus SOC alone were 2.8 percent versus 4.0 percent for new onset diabetes, 0.4 percent versus 0 percent for neurocognitive events, and 4.7 percent versus 8.5 percent for muscle- related events. The percentage of patients who discontinued Repatha due to AEs was 0.5 percent in year four and 2.8 percent in year one. Additionally, no neutralizing antibodies and only four transient binding antibody cases were observed.¹

Cardiovascular disease is the leading cause of death worldwide.² In the U.S., there are approximately 11 million people with atherosclerotic cardiovascular disease (ASCVD) and/or familial hypercholesterolemia (FH) who have uncontrolled levels of LDL-C over 70 mg/dL, despite treatment with statins or other cholesterol-lowering therapies.^3,4

OSLER-1 Study Design

Open Label Study of Long TERm Evaluation Against LDL-C 1 (OSLER-1) is an open-label extension study with Repatha, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. The study is being conducted across 192 sites in 18 countries.

Patients were eligible to enroll in OSLER-1 study after completing one of the double-blind Phase 2 parent studies without experiencing a serious AE requiring treatment discontinuation. During the first year patients were randomized 2:1 to Repatha 420 mg monthly in addition to SOC or SOC alone. After year one, all patients continuing in the study received Repatha 420 mg monthly in addition to SOC. Lipid parameters, safety and tolerability were assessed every 12 weeks.

The primary objective of this analysis is to evaluate whether LDL-C reductions with Repatha persist across different populations during an extended period of time. The secondary objective included the assessment of AEs, anti-drug antibodies (ADAs), and factors contributing to treatment discontinuation.

About Repatha (evolocumab)

Repatha (evolocumab) is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.⁵

Repatha is approved in more than 40 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.